Serum protein binding of diazepam, desmethyldiazepam, furosemide, indomethacin, warfarin, and phenobarbital in human fetus, mother, and newborn infant

The protein binding of diazepam, desmethyldiazepam, furosemide, indomethacin, warfarin, and phenobarbital in maternal and fetal cord serum at the time of birth, and in serum of neonates between 1 and 11 days of age was studied. The protein binding of diazepam and desmethyldiazepam was higher in the fetus than in the mother, thus explaining the fetal cumulation of these drugs in vivo. After birth, both drugs were partially displaced from neonatal binding sites. The decreased protein binding capacity in the mother and the neonate related to increased free fatty-acid levels. The pattern of protein binding of warfarin in the groups investigated was a mirror image of those of diazepam and its metabolite. The protein binding of indomethacin progressively decreased in the neonate during the first two postnatal weeks, while that of furosemide remained at lowered levels throughout this time interval. The protein binding of phenobarbital was similar in the groups investigated. Our results suggest that drugs such as diazepam, which can be displaced from binding sites by free fatty acids, may cumulate in the fetus and may exhibit much decreased protein binding and possibly unexpectedly strong effects in the neonate after birth.     

Detection of microscopic disease: comparing histology, immunocytology, and RT-PCR of tyrosine hydroxylase, GAGE, and MAGE

BACKGROUND: We first explored the use of multiple molecular markers to overcome tumor heterogeneity. Sixty-seven neuroblastoma (NB) tumors were tested for the expression of GAGE, MAGE-2, MAGE-2, MAGE-3, and MAGE-4 by RT-PCR and then chemiluminescence; 82% of tumors had detectable GAGE, and 88% expressed at least one of the four MAGE genes. PROCEDURE AND RESULTS: By combining GAGE and MAGE, 64 of 67 (95%) of tumors became detectable; 17 of 67 coexpressed all five molecular markers. Neither GAGE nor MAGE expression correlated with stage. GAGE was found to have the broadest (18 of 18) expression among stage 4 tumors. Two hundred fifty-nine bone marrows from 99 patients were then studied for NB positivity by four detection methods: histology, immunocytology, and molecular detection by GAGE and tyrosine hydroxylase (TH) mRNA. Two hundred seven samples were NB-positive by one detection method. All four techniques were comparable in detecting tumor cells at diagnosis and at relapse. GAGE and immunocytology were far more sensitive than histology and TH mRNA when marrows were sampled during chemotherapy and at the time of clinical remission. CONCLUSIONS: By combining multiple molecular markers and independent screening techniques, we may be able to overcome tumor heterogeneity and expedite the detection of microscopic disease in the clinical management of neuroblastoma.     

Concentrations of Fe, K, Na, Ca, P, Zn and Mg in maternal colostrum and mature milk

The objective of this study was to determine the concentrations of Fe, K, Na, Ca, P, Zn and Mg in colostrum and mature milk (2 months) from nursing mothers, and the correlation between the concentration of these micronutrients and newborn weight, maternal age, gestational age GA, inter-pregnancy interval, and gestational weight gain. Thirty one women donated milk on the 2nd postpartum day and on the 2nd month of lactation. Micronutrients were analysed by atomic emission spectrophotometry. The concentrations (mean+/-SD) of Fe (0.12+/-0.08; 0.09+/-0.5 mg/100 ml), Zn (0.93+/-0.36; 0.15+/-0.06 mg/100 ml), K (62.8+/-11.5; 46.2+/-0.84 mg/100 ml) and Na (33.3+/-12.3; 20.5+/-15.6 mg/100 ml) decreased from colostrum to mature milk, whereas Ca (21.4+/-5.8; 25.0+/-3.1 mg/100 ml) and P (11.12+/-2.8; 13.7+/-2.0 mg/100 ml) increased. Correlations were observed between Zn and Ca concentrations and GA (r=-0.41, p=0.042; r=0.48, p=0.014, respectively), between Ca and K and inter-pregnancy interval (r=0.56, p=0.001; r=0.38, p=0.033, respectively), and between Mg and P and maternal age (r=0.49, p=0.005; r=0.37, p=0.042, respectively). The Zn concentration in colostrum showed a negative correlation with gestational weight gain (r=-0.49, p=0.006), and Na concentration showed a negative correlation with newborn weight (r=-0.38, p=0.036). The concentration of micronutrients in colostrum and mature milk (2 months) suffers alterations, including a decrease in Fe, Zn, K and Na and an increase in Ca and P, probably in order to satisfy the requirements of the nursing infant. Micronutrients are influenced by birth weight, maternal age, gestational weight gain, GA and inter-pregnancy interval.     

Stability and change of attachment at 14, 24, and 58 months of age: behavior, representation, and life events

Stability and change of attachment was examined longitudinally in a group of 48 children at 14, 24, and 58 months of age. Whereas attachment classifications showed stability between 14 and 24 months, lack of stability was the case between either 14 or 24 months and 58 months. Mothers of children who did not exhibit stability of attachment reported more negative and less positive life events. No correspondence was found between attachment classification at 14 or 24 months and mental representations at 58 months. However there was agreement between representational and behavioral measures of attachment at 58 months, where mental representations of attachment appeared to mirror and complement behavioral classification of the attachment relationship with the mother. Evidence for continuity of attachment from infancy to childhood internal representations was found only in a subgroup of children who showed stability of secure attachment between infancy and 58 months of age. These children exhibited greater Emotional Openness in the SAT at 4.5 years. Findings are discussed in terms of different positions in attachment theory and research regarding the stability and change of attachment relationships.     

Neuropsychology and genetics of speech, language, and literacy disorders

The authors review the neuropsychology, brain bases, and genetics of three related disorders of language development: reading disability, or developmental dyslexia (RD); language impairment (LI); and speech sound disorder (SSD). Over the past three decades, cognitive analysis has demonstrated that the reading difficulties of most children who have RD result from phonologic impairments (difficulties processing the sound structure of language). Although understanding of LI and SSD is somewhat less developed, both disorders are also associated with phonologic impairments, which may account for their comorbidity with RD. Research across levels of analysis is progressing rapidly to promote understanding not only of each disorder by itself but also of the relationships of the three disorders to each other.